Graves Orbitopathy, Thyroid Eye Disease, TED
Conditions
Keywords
Thyroid Eye Disease, TED, Graves Orbitopathy, Graves' Disease, Hashimoto's thyroiditis
Brief summary
The goal of this clinical trial is to evaluate the efficacy, safety, and tolerability of linsitinib in participants with moderate to severe Thyroid Eye Disease (TED).
Interventions
DRUGlinsitinib
150 mg linsitinib is taken twice daily by mouth for 24 weeks
DRUGPlacebo
0 mg placebo taken twice daily by mouth for 24 weeks
Sponsors
Sling Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants must be ≥ 18 years of age at Screening 2. Clinical diagnosis of Graves' Disease and/or autoimmune Hashimoto's thyroiditis associated with active moderate to severe TED with a CAS ≥ 3 (on the 7-item scale) for the most severely affected eye (primary study eye) at Screening and Baseline. 3. Moderate to severe active TED (not sight-threatening but has an appreciable impact on daily life), with diagnosis of TED within 15 months prior to the Screening visit and usually associated with 1 or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, proptosis ≥ 3 mm above normal for race and gender, and/or inconstant or constant diplopia. 4. Participants must be euthyroid with the participant's baseline disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine \[FT4\] and free triiodothyronine levels \[FT3\] \< 50% above or below the normal limits of the central laboratory) at Screening. 5. Does not require immediate ophthalmic surgery, radiotherapy to orbits or other ophthalmological intervention at the time of Screening and is not planning for any such treatment during the course of the study.
Exclusion criteria
1. Any progressing optic neuropathy due to TED that has worsened in the last 6 months in the opinion of the investigator. 2. Corneal decompensation unresponsive to medical management. 3. Previous orbital irradiation or orbital surgery in either eye. 4. Any glucocorticoid use (IV or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone or equivalent for the treatment of TED within 8 weeks of Screening. 5. Prior IGF-1R inhibitor therapy for any condition.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure percentage of participants who are Proptosis Responders at Week 24 | 24 weeks | The proptosis responder rate is the percentage of participants with a ≥ 2 mm reduction of proptosis from Baseline in the primary study eye without deterioration (≥ 2 mm increase) of proptosis in the contralateral non-study eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from Baseline in Proptosis to Week 24 | 24 Weeks | Evaluate the effect of linsitinib 150 mg twice daily versus placebo on the mean change from Baseline to Week 24 in proptosis measurement in the primary study eye. |
| Evaluate the effect of linsitinib 150 mg twice daily versus placebo on the overall responder rate at Week 24 | 24 Weeks | Overall responder rate (percentage of participants with ≥ 2-point reduction in 7 point CAS and ≥ 2 mm reduction in proptosis from Baseline in the primary study eye), provided there is no corresponding deterioration (≥ 2-point/mm increase) in CAS or proptosis in the contralateral non-study eye at Week 24. |
| Evaluate the effect of linsitinib 150 mg twice daily versus placebo on the mean change from Baseline to Week 24 in the GO-QoL questionnaire overall score. | 24 Weeks | Mean change from Baseline to Week 24 in the Graves' Orbitopathy Quality of Life questionnaire (GO-QoL) questionnaire overall score (0-100 where higher scores are a better outcome). |
| Evaluate the effect of linsitinib 150 mg twice daily versus placebo on the percentage of participants with a CAS value of 0 or 1 at Week 24 in the primary study eye. | 24 Weeks | Percentage of participants with a CAS value of 0 or 1 at Week 24 in the primary study eye. |
Countries
United States
Contacts
CONTACTCathy Radovich
Outcome results
None listed